antiangiogenic

Low-dose metronomic cisplatin as an antiangiogenic and anti-inflammatory strategy for cancer

Posted by

0


Abstract

Background

Conventional chemotherapy is based on the maximum tolerated dose (MTD) and requires treatment-free intervals to restore normal host cells. MTD chemotherapy may induce angiogenesis or immunosuppressive cell infiltration during treatment-free intervals. Low-dose metronomic (LDM) chemotherapy is defined as frequent administration at lower doses and causes less inflammatory change, whereas MTD chemotherapy induces an inflammatory change. Although several LDM regimens have been applied, LDM cisplatin (CDDP) has been rarely reported. This study addressed the efficacy of LDM CDDP on tumour endothelial cell phenotypic alteration compared to MTD CDDP.

Methods

Tumour growth and metastasis were assessed in bladder cancer-bearing mice treated with LDM or MTD gemcitabine (GEM) and CDDP. To elucidate the therapeutic effects of LDM CDDP, the change of tumour vasculature, tumour-infiltrating immune cells and inflammatory changes were evaluated by histological analysis and mRNA expression in tumour tissues.

Results

Tumour growth and bone metastasis were more suppressed by LDM CDDP + MTD GEM treatment than MTD CDDP + MTD GEM. Myeloid­derived suppressor cell accumulation was reduced by LDM CDDP, whereas inflammatory change was induced in the tumour microenvironment by MTD CDDP.

Conclusion

LDM CDDP does not cause inflammatory change unlike MTD CDDP, suggesting that it is a promising strategy in chemotherapy.

Quercetin, a dietary-derived flavonoid, possesses antiangiogenic potential

Posted by

0


Abstract

Quercetin, a dietary-derived flavonoid, suppresses tumor growth in vitro and in vivo, and inhibits the activity of tyrosine kinase. The effects of quercetin on the angiogenic process were examined in this study. Quercetin was found to inhibit several important steps of angiogenesis including proliferation, migration, and tube formation of human microvascular dermal endothelial cells in a dose-dependent manner. Additionally, the effect of quercetin on endothelial cell proliferation was confirmed using human umbilical vein endothelial cells. The activity of quercetin on the proliferation of endothelial cells was stronger than that on A549, BEL-7402, MKN-45 tumor cells and NIH-3T3 fibroblast cells. The chicken chorioallantoic membrane assay revealed that addition of quercetin displayed an antiangiogenic effect in vivo. After exposure to quercetin, a decrease in the expression and activity of matrix metalloproteinase-2, which is involved in the angiogenic process of migration, invasion, and tube formation, was observed by reverse transcription-polymerase chain reaction (RT-PCR) and gelatin zymography. These findings suggest that quercetin has antiangiogenic potential and that this effect may be related to an influence on the expression and activity of matrix metalloproteinase-2.